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Environmental fate & pathways

Hydrolysis

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Endpoint:
hydrolysis
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is readily biodegradable
Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
16 April 1993 - 12 May 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study was conducted to assess the stability of DBM under physiological conditions. This test design differs from the one for the evaluation of the abiotic stability under environmental conditions regarding test temperature and pH values. Therefore, this study is regarded as supporting information.
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
yes (incl. QA statement)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products:
- pH 1.2: 11 samples within 144 hours
- pH 4: 11 samples within 144 hours at 20 and 37°C
- pH 7: 11 samples within 144 hours at 20 and 37°C; 10 samples within 136 hours at 61.5°C; 16 samples within 24 hours at 81.2°C; 14 samples
within 6 hours at 97.6°C
- pH 9: 17 samples within 192 hours at 20 and 37°C
- Sampling method: autosampler (Maraton (Sun Chrom GmbH))
Buffers:
- pH: 1.2
- Type and final molarity of buffer: 0.1 M KCl
- Composition of buffer: 7.46 g KCl/l water, adjusted with HCl to pH 1.2

- pH: 4.0
- Type and final molarity of buffer: 0.1 M KH2PO4
- Composition of buffer: 13.61 g KH2PO4/l water, adjusted with HCl to pH 4.0

- pH: 7.0
- Type and final molarity of buffer: 0.1 M KH2PO4
- Composition of buffer: 13.61 g KH2PO4/l water, adjusted with HCl to pH 7.0

- pH: 9.0
- Type and final molarity of buffer: 0.1 M KCl/H3BO3
- Composition of buffer: 7.46 g KCl + 6.18 g H3BO3/l water, adjusted with NaOH to pH 9.0
Estimation method (if used):
For the method validation, the calculations were carried out by using the PLOTIT software (ver. 1.6, Scientific Programming Enterprises, USA)
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: autosampling vials
- Sterilisation method: none, aqua ad injectabilia, sterile and pyrogen-free was used
Duration:
144 h
pH:
1.2
Temp.:
37 °C
Initial conc. measured:
22.8 mg/L
Duration:
144 h
pH:
4
Temp.:
20 °C
Initial conc. measured:
23.99 mg/L
Duration:
144 h
pH:
4
Temp.:
37 °C
Initial conc. measured:
24.62 mg/L
Duration:
144 h
pH:
7
Temp.:
20 °C
Initial conc. measured:
24.53 mg/L
Duration:
144 h
pH:
7
Temp.:
37 °C
Initial conc. measured:
21.19 mg/L
Duration:
136 h
pH:
7
Temp.:
61.5 °C
Initial conc. measured:
26.68 mg/L
Duration:
24 h
pH:
7
Temp.:
81.2 °C
Initial conc. measured:
26.9 mg/L
Duration:
6 h
pH:
7
Temp.:
97.6 °C
Initial conc. measured:
27.58 mg/L
Duration:
192 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
23.76 mg/L
Duration:
192 h
pH:
9
Temp.:
37 °C
Initial conc. measured:
24.13 mg/L
Number of replicates:
pH 1.2: 2
pH 4: 1 (20°C), 2 (37°C)
pH 7: 1 (20°C), 2 (37°C), 2 (61.5°C), 2 (81.2°C), 2 (97.6°C)
pH 9: 1 (20°C), 2 (37°C)
Positive controls:
no
Negative controls:
no
Transformation products:
not measured
pH:
1.2
Temp.:
37 °C
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: after 144 hours, dibutyl maleinate was hydrolysed to a yield of 15%
pH:
4
Temp.:
37 °C
DT50:
> 0.5 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: no significant degradation observed
pH:
7
Temp.:
20 °C
Hydrolysis rate constant:
0.007 h-1
DT50:
96.3 h
St. dev.:
0.4
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r² = 0.997
pH:
7
Temp.:
37 °C
Hydrolysis rate constant:
0.062 h-1
DT50:
11.2 h
St. dev.:
4.1
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r² = 0.997
pH:
7
Temp.:
25 °C
DT50:
2 870 h
Type:
other: Arrhenius equation
Remarks on result:
other: extrapolated value. DT50 corresponds to about 4 month
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0.014 h-1
DT50:
50 h
Type:
other: Arrhenius equation
Remarks on result:
other: extrapolated value
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
Validity criteria fulfilled:
yes

Description of key information

Read-across from dibutyl maleinate:

pH 1.2, 37°C, 144 hours: about 15% degradation
pH 4, 37°C: no significant degradation observed
pH 7, 20°C: DT50 = 96.3 hours
pH 7, 37°C: DT50 = 11.2 hours
pH 9, 25°C: DT50 = 50 hours

Key value for chemical safety assessment

Half-life for hydrolysis:
96.3 h
at the temperature of:
20 °C

Additional information

A study on hydrolysis for bis(2ethylhexyl)maleinate is not needed as the substance is readily biodegradable. As supporting information,data

were taken for read-across from a structural similar diester of maleic acid, dibutyl maleinate. The results of the hydrolysis study on dibutyl maleinate indicate an increase of hydrolysis with increasing pH. Whereas under acidic conditions only a low degradation of dibutyl maleinate was observed, the degree of degradation increased with increasing pH. Under the test conditions which approximately correspond to environmental conditions, i.e. a pH value of 7 and a water temperature of 20°C, a DT50 of about 96.3 hours was observed. Based on the structural similarity of dibutyl- and bis(2ethylhexyl)maleinate it is assumed that the hydrolytical pathway of bis(2ethylhexyl)maleinate is comparable to the one of dibutyl maleinate: The hydrolytical cleavage of the ester bounds will result in the formation of maleic acid and two alcohol moieties.